A new rat model of chronic cerebral hypoperfusion associated with arteriovenous malformations

Restricted access

Object. A new experimental model of chronic cerebral hypoperfusion was developed to study the effects of systemic arterial shunting and obstruction of the primary vessel that drains intracranial venous blood on cerebral perfusion pressure (CPP), as well as cerebral pathological changes during restoration of normal perfusion pressure.

Methods. Twenty-four Sprague—Dawley rats were randomly assigned to either a sham-operated group, an arteriovenous fistula (AVF) group, or a model group (eight rats each). The animal model was readied by creating a fistula through an end-to-side anastomosis between the right distal external jugular vein (EJV) and the ispilateral common carotid artery (CCA), followed by ligation of the left vein draining the transverse sinus and bilateral external carotid arteries. Systemic mean arterial pressure (MAP), draining vein pressure (DVP), and CPP were monitored and compared among the three groups preoperatively, immediately postoperatively, and again 90 days later. Following occlusion of the fistula after a 90-day interval, blood—brain barrier (BBB) disruption and water content in the right cortical tissues of the middle cerebral artery territory were confirmed and also quantified with transmission electron microscopy.

Formation of a fistula resulted in significant decreases in MAP and CPP, and a significant increase in DVP in the AVF and model groups. Ninety days later, there were still significant increases in DVP and decreases in CPP in the model group compared with the other groups (p < 0.05). Damage to the BBB and brain edema were noted in animals in the model group during restoration of normal perfusion pressure by occlusion of the fistula. Electron microscopy studies revealed cerebral vasogenic edema and/or hemorrhage in various amounts, which correlated with absent astrocytic foot processes surrounding some cerebral capillaries.

Conclusions. The results demonstrated that an end-to-side anastomosis between the distal EJV and CCA can induce a decrease in CPP, whereas a further chronic state of cerebral hypoperfusion may be caused by venous outflow restriction, which is associated with perfusion pressure breakthrough. This animal model conforms to the basic hemodynamic characteristics of human cerebral arteriovenous malformations.

Article Information

Contributor Notes

Address reprint requests to: Jian Hai, M.D., Department of Neurosurgery, Tongji Hospital, Tongji University, 389 XinCun Road, Shanghai 200065, People's Republic of China. email: haijianl@163.com.
Headings
References
  • 1.

    Al-Rodhan NRFSundt TM JrPiepgras DGet al: Occlusive hyperemia: a theory for the hemodynamic complications following resection of intracerebral arteriovenous malformations. J Neurosurg 78:1671751993Al-Rodhan NRF Sundt TM Jr Piepgras DG et al: Occlusive hyperemia: a theory for the hemodynamic complications following resection of intracerebral arteriovenous malformations. J Neurosurg 78:167–175 1993

    • Search Google Scholar
    • Export Citation
  • 2.

    Awad IAMagdinec MSchubert A: Intracranial hypertension after resection of cerebral arteriovenous malformations: predisposing factors and management stratgy. Stroke 25:6116231994Awad IA Magdinec M Schubert A: Intracranial hypertension after resection of cerebral arteriovenous malformations: predisposing factors and management stratgy. Stroke 25:611–623 1994

    • Search Google Scholar
    • Export Citation
  • 3.

    Bakay LSweet WH: Cervical and intracranial intraarterial pressures with and without vascular occlusion. Surg Gynecol Obstet 95:67751952Bakay L Sweet WH: Cervical and intracranial intraarterial pressures with and without vascular occlusion. Surg Gynecol Obstet 95:67–75 1952

    • Search Google Scholar
    • Export Citation
  • 4.

    Bederson JBWiestler ODBrüstle Oet al: Intracranial venous hypertension and the effects of venous outflow obstruction in a rat model of arteriovenous fistula. Neurosurgery 29:3413501991Bederson JB Wiestler OD Brüstle O et al: Intracranial venous hypertension and the effects of venous outflow obstruction in a rat model of arteriovenous fistula. Neurosurgery 29:341–350 1991

    • Search Google Scholar
    • Export Citation
  • 5.

    Belayev LBusto RZhao Wet al: Quantitative evaluation of blood-brain barrier permeability following middle cerebral artery occlusion in rats. Brain Res 739:88961996Belayev L Busto R Zhao W et al: Quantitative evaluation of blood-brain barrier permeability following middle cerebral artery occlusion in rats. Brain Res 739:88–96 1996

    • Search Google Scholar
    • Export Citation
  • 6.

    Billet AQueral LAPolito WFet al: The vascular steal phenomenon: an experimental model. Surgery 96:9239281984Billet A Queral LA Polito WF et al: The vascular steal phenomenon: an experimental model. Surgery 96:923–928 1984

    • Search Google Scholar
    • Export Citation
  • 7.

    Kader AYoung WL: The effects of intracranial arteriovenous malformations on cerebral hemodymamics. Neurosurg Clin N Am 7:7677811996Kader A Young WL: The effects of intracranial arteriovenous malformations on cerebral hemodymamics. Neurosurg Clin N Am 7:767–781 1996

    • Search Google Scholar
    • Export Citation
  • 8.

    Langer DJLasner TMHurst RWet al: Hypertension, small size, and deep venous drainage are associated with risk of hemorrhagic presentation of cerebral arteriovenous malformations. Neurosurgery 42:4814891998Langer DJ Lasner TM Hurst RW et al: Hypertension small size and deep venous drainage are associated with risk of hemorrhagic presentation of cerebral arteriovenous malformations. Neurosurgery 42:481–489 1998

    • Search Google Scholar
    • Export Citation
  • 9.

    Mansmann UMeisel JBrock Met al: Factors associated with intracranial hemorrhage in cases of cerebral arteriovenous malformation. Neurosurgery 46:2722812000Mansmann U Meisel J Brock M et al: Factors associated with intracranial hemorrhage in cases of cerebral arteriovenous malformation. Neurosurgery 46:272–281 2000

    • Search Google Scholar
    • Export Citation
  • 10.

    Mast HMohr JPOsipov Aet al: ‘Steal’ is an unestablished mechanism for the clinical presentation of cerebral arteriovenous malformations. Stroke 26:121512201995Mast H Mohr JP Osipov A et al: ‘Steal’ is an unestablished mechanism for the clinical presentation of cerebral arteriovenous malformations. Stroke 26:1215–1220 1995

    • Search Google Scholar
    • Export Citation
  • 11.

    Matsuo YOnodera HShiga Yet al: Correlation between myeloperoxidase-quantified neutrophil accumulation and ischemic brain injury in the rat. Effects of neutrophil depletion. Stroke 25:146914751994Matsuo Y Onodera H Shiga Y et al: Correlation between myeloperoxidase-quantified neutrophil accumulation and ischemic brain injury in the rat. Effects of neutrophil depletion. Stroke 25:1469–1475 1994

    • Search Google Scholar
    • Export Citation
  • 12.

    Meyer BSchaller CFrenkel Cet al: Distributions of local oxygen saturation and its response to changes of mean arterial blood pressure in the cerebral cortex adjacent to arteriovenous malformations. Stroke 30:262326301999Meyer B Schaller C Frenkel C et al: Distributions of local oxygen saturation and its response to changes of mean arterial blood pressure in the cerebral cortex adjacent to arteriovenous malformations. Stroke 30:2623–2630 1999

    • Search Google Scholar
    • Export Citation
  • 13.

    Miyasaka YKurata ATokiwa Ket al: Draining vein pressure increases and hemorrhage in patients with arteriovenous malformation. Stroke 25:5045071994Miyasaka Y Kurata A Tokiwa K et al: Draining vein pressure increases and hemorrhage in patients with arteriovenous malformation. Stroke 25:504–507 1994

    • Search Google Scholar
    • Export Citation
  • 14.

    Morgan MKAnderson RESundt TM Jr: The effects of hyperventilation on cerebral blood flow in the rat with an open and closed carotid-jugular fistula. Neurosurgery 25:6066121989Morgan MK Anderson RE Sundt TM Jr: The effects of hyperventilation on cerebral blood flow in the rat with an open and closed carotid-jugular fistula. Neurosurgery 25:606–612 1989

    • Search Google Scholar
    • Export Citation
  • 15.

    Morgan MKAnderson RESundt TM Jr: A model of the pathophysiology of cerebral arteriovenous malformations by a carotid-jugular fistula in the rat. Brain Res 496:2412501989Morgan MK Anderson RE Sundt TM Jr: A model of the pathophysiology of cerebral arteriovenous malformations by a carotid-jugular fistula in the rat. Brain Res 496:241–250 1989

    • Search Google Scholar
    • Export Citation
  • 16.

    Morgan MKJohnston IBesser Met al: Cerebral arteriovenous malformations, steal, and the hypertensive breakthrough threshold. An experimental study in rats. J Neurosurg 66:5635671987Morgan MK Johnston I Besser M et al: Cerebral arteriovenous malformations steal and the hypertensive breakthrough threshold. An experimental study in rats. J Neurosurg 66:563–567 1987

    • Search Google Scholar
    • Export Citation
  • 17.

    Morgan MKSekhon LHSFinfer Set al: Delayed neurological deterioration following resection of arteriovenous malformations of the brain. J Neurosurg 90:6957011999Morgan MK Sekhon LHS Finfer S et al: Delayed neurological deterioration following resection of arteriovenous malformations of the brain. J Neurosurg 90:695–701 1999

    • Search Google Scholar
    • Export Citation
  • 18.

    Nussbaum ESHeros RCMadison MTet al: The pathogenesis of arteriovenous malformations: insights provided by a case of multiple arteriovenous malformations developing in relation to developmental venous anomaly. Neurosurgery 43:3473521998Nussbaum ES Heros RC Madison MT et al: The pathogenesis of arteriovenous malformations: insights provided by a case of multiple arteriovenous malformations developing in relation to developmental venous anomaly. Neurosurgery 43:347–352 1998

    • Search Google Scholar
    • Export Citation
  • 19.

    Sakaki TTsujimoto SNishitani Met al: Perfusion pressure breakthrough threshold of cerebral autoregulation in the chronically ischemic brain: an experimental study in cats. J Neurosurg 76:4784851992Sakaki T Tsujimoto S Nishitani M et al: Perfusion pressure breakthrough threshold of cerebral autoregulation in the chronically ischemic brain: an experimental study in cats. J Neurosurg 76:478–485 1992

    • Search Google Scholar
    • Export Citation
  • 20.

    Sekhon LHSMorgan MKSpence I: Normal perfusion pressure breakthrough: the role of capillaries. J Neurosurg 86:5195241997Sekhon LHS Morgan MK Spence I: Normal perfusion pressure breakthrough: the role of capillaries. J Neurosurg 86:519–524 1997

    • Search Google Scholar
    • Export Citation
  • 21.

    Sekhon LHSMorgan MKSpence Iet al: Chronic cerebral hypoperfusion: pathological and behavioral consequences. Neurosurgery 40:5485561997Sekhon LHS Morgan MK Spence I et al: Chronic cerebral hypoperfusion: pathological and behavioral consequences. Neurosurgery 40:548–556 1997

    • Search Google Scholar
    • Export Citation
  • 22.

    Spetzler RFWilson CBWeinstein Pet al: Normal perfusion pressure breakthrough theory. Clin Neurosurg 25:6516721978Spetzler RF Wilson CB Weinstein P et al: Normal perfusion pressure breakthrough theory. Clin Neurosurg 25:651–672 1978

    • Search Google Scholar
    • Export Citation
  • 23.

    Wilson CBHieshima G: Occlusive hyperemia: a new way to think about an old problem. J Neurosurg 78:1651661993Wilson CB Hieshima G: Occlusive hyperemia: a new way to think about an old problem. J Neurosurg 78:165–166 1993

    • Search Google Scholar
    • Export Citation
  • 24.

    Yamada MMiyasaka YIrikura Ket al: A canine model of intracranial arteriovenous shunt with acute cerebral venous hypertension. Neurol Res 20:73781998Yamada M Miyasaka Y Irikura K et al: A canine model of intracranial arteriovenous shunt with acute cerebral venous hypertension. Neurol Res 20:73–78 1998

    • Search Google Scholar
    • Export Citation
  • 25.

    Young WLKader AOrnstein Eet al: Cerebral hyperemia after arteriovenous malformation resection is related to “breakthrough” complications but not to feeding artery pressure. The Columbia University Arteriovenous Malformation Study Project. Neurosurgery 38:108510951996Young WL Kader A Ornstein E et al: Cerebral hyperemia after arteriovenous malformation resection is related to “breakthrough” complications but not to feeding artery pressure. The Columbia University Arteriovenous Malformation Study Project. Neurosurgery 38:1085–1095 1996

    • Search Google Scholar
    • Export Citation
TrendMD
Cited By
Metrics

Metrics

All Time Past Year Past 30 Days
Abstract Views 175 160 11
Full Text Views 170 97 1
PDF Downloads 113 35 1
EPUB Downloads 0 0 0
PubMed
Google Scholar